Primate cone photoreceptors produce large oscillatory photocurrents in response to light excitation. These are not seen in primate rods and in fact have only otherwise been seen in human cones. A negative feedback loop regulating [cGMP] is known to exist in amphibian photoreceptors, with Ca2+ acting to stabilize the dark current, assist recovery of the light response, and control light adaptation. Similar regulation is believed to occur in mammalian cells and may be the cause of the oscillatory responses of primate cones. It is this possibility that we are trying to investigate. Since it is the current in the light-sensitive channels that is oscillatory, the oscillation may result from changes in the membrane potential or from feedback regulation of cGMP levels. We have successfully developed conditions to enzymatically isolate cone photoreceptors that continue to respond to light. Preliminary results from voltage-clamped cones indicate that photocurrent oscillations persist even when the influence of driving forces changes is eliminated by holding the voltage constant. This implicates [cGMP] regulation in the generation of the oscillations and suggest an interaction between Ca2+ and cyclic GMP levels. The role of Ca2+ will be examined by recording from cones perfused in low-Ca2+:zero-Na+ Ringers, which clamps the internal Ca2+ concentration. This should block the oscillation if Ca2+ changes are involved in producing it. The effect of the rate of change of internal Ca2+ will be examined by recording from cones perfused in BAPTA/AM. This should slow intracellular Ca2+ kinetics and alter oscillation kinetics if Ca2+ is the feedback regulator. These results should allow us to assess the role of Ca2+ changes in producing the oscillatory responses of cones, helping us to understand how the feedback loop in cones works and differs from that of rods. *KEY*Retina, Photoreceptors, Phototransduction, Calcium